A General Approach for Fluoroalkylation of O-Nucleophiles with Monofluoroalkylated Sulfonium Ylides†

The development of a series of shelf-stable monofluoroalkylated sulfonium ylide reagents and their reactions with a variety of O-nucleophiles including phenols, sulfonic acids, carboxylic acids, 1-hydroxy-benzotrizoles, amino acids was described. In general, monofluoroakylated sulfonium ylides were synthesized in three steps from commercially available starting materials including thiophenols, alkyl halides and dimethyl 2-diazomalonate. Reactions with the O-nucleophiles occurred under mild conditions and afforded the corresponding monofluoroalkylated ethers, sulfonates, and esters in good to excellent yields, thus providing a robust approach for the preparation of these compounds. Further expansion of monofluoroalkylation of C-terminus of peptides potentially provided modified drug-like peptides.